Department of Orthopaedics, Huaihe Hospital of Henan University, Kaifeng, China.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Cell Biol. 2020 Feb 12;40(5). doi: 10.1128/MCB.00362-19.
Osteomyelitis, an infection of the bone and bone marrow, imposes a heavy burden on public health care systems owing to its progressive bone destruction and sequestration. Human bone mesenchymal stem cells (hBMSCs) play a key role in the process of bone formation, and mounting evidence has confirmed that long noncoding RNAs (lncRNAs) are involved in hBMSC osteogenic differentiation. Nevertheless, the exact function and molecular mechanism of lncRNAs in osteogenic differentiation during osteomyelitis development remain to be explored. In this study, hBMSCs were treated with staphylococcal protein A (SpA) during osteogenic differentiation induction to mimic osteomyelitis The results of lncRNA microarray analysis revealed that FAM83H-AS1 presented the lowest expression among the significantly downregulated lncRNAs. Functionally, ectopic expression of FAM83H-AS1 contributed to osteogenic differentiation of SpA-induced hBMSCs. Additionally, our findings revealed that FAM83H-AS1 negatively regulated microRNA 541-3p (miR-541-3p), and WNT3A was validated as a target gene of miR-541-3p. Mechanically, FAM83H-AS1 elevated WNT3A expression by competitively binding with miR-541-3p. Lastly, it was demonstrated that FAM83H-AS1/miR-541-3p/WNT3A ameliorated SpA-mediated inhibition of the osteogenic differentiation of hBMSCs, which provided a novel therapeutic strategy for patients with osteomyelitis.
骨髓炎是一种骨骼和骨髓的感染，由于其进行性的骨破坏和隔离，给公共医疗保健系统带来了沉重的负担。人骨髓间充质干细胞（hBMSCs）在骨形成过程中起着关键作用，越来越多的证据证实长非编码 RNA（lncRNA）参与 hBMSC 成骨分化。然而，lncRNA 在骨髓炎发展过程中成骨分化中的确切功能和分子机制仍有待探索。在这项研究中，在成骨分化诱导过程中用葡萄球菌蛋白 A（SpA）处理 hBMSC 以模拟骨髓炎。lncRNA 微阵列分析的结果表明， FAM83H-AS1 在显著下调的 lncRNA 中表达最低。功能上，FAM83H-AS1 的异位表达促进了 SpA 诱导的 hBMSC 的成骨分化。此外，我们的研究结果表明， FAM83H-AS1 负调控 microRNA 541-3p（miR-541-3p），并且 WNT3A 被验证为 miR-541-3p 的靶基因。机制上， FAM83H-AS1 通过与 miR-541-3p 竞争结合来提高 WNT3A 的表达。最后，证明 FAM83H-AS1/miR-541-3p/WNT3A 改善了 SpA 介导的 hBMSC 成骨分化抑制，为骨髓炎患者提供了一种新的治疗策略。
